The objective of the studies outlined in this proposal is to define the functional anatomical basis for the neural and endocrine mechanisms involved in the regulation of gastric mucosal functions. These studies will be carried out on tissues from experimental animals and, when feasible, also from human gastrectomy specimens. The specific aims of this study are: a) to determine the anatomic relationship of nerves with secretory and endocrine-paracrine cells of the gastric mucosa; b) to identify the neuropeptides present in these nerves and determine if there is selectivity in their distribution; c) to determine whether and which neuropeptides are in perivascular nerves of the gastric mucosa; d) to determine the anatomic relationships between the somatostatin-producing cells and their target cells in the gastric mucosa; e) to determine if granuliberin, a histamine releasing peptide from frog stomach, is also present in cells and/or nerves of the gastric mucosa; f) to determine if granuliberin influences the function of different types of histaminocytes in vitro; and g) to trace and identify the neurons from which gastric mucosal nerves originate. The main experimental approaches include histochemistry, immunohistochemistry, and electron microscopy. Peptide extraction and radioimmunoassay, as well as assay for histamine and histidine decarboxylase will be carried out in some of the experiments. Fulfilling the objective of this proposal will result in a better understanding of the normal regulation of gastric mucosal functions by neural and endocrine mechanisms. This, in turn, would be the basis for enhanced insights on the nature and pathways of pathologic changes leading to peptic ulcer disease and would provide a rationale for the treatment of this disease based on the full understanding of its pathophysiology.